Epidemiology and Treatment Outcomes of Voriconazole-Induced Invasive Cutaneous Squamous Cell Carcinoma in Japanese Patients with Pulmonary Aspergillosis.

Objectives: Voriconazole is a broad-spectrum antifungal agent known to be associated with cutaneous squamous cell carcinoma (cSCC) in White organ transplant recipients; however, such cases are rarely reported in Asian populations. This study aimed to examine the epidemiology and treatment outcomes of Japanese patients without a history of organ transplantation who developed invasive cSCC during voriconazole therapy. Methods: This retrospective observational study analyzed data from six Japanese male patients who were treated at our hospital between the years 2013 and 2023. All patients had Fitzpatrick skin type IV and were undergoing long-term voriconazole therapy for pulmonary aspergillosis. The diagnosis of invasive cSCC was confirmed via skin biopsy. Clinical, pathological, and treatment data were collected and analyzed descriptively. Results: Fifteen facial lesions were identified (nine at initial presentation and six during follow-up). The median duration of voriconazole treatment before cSCC diagnosis was 66.5 months. Tumors had a median diameter of 17 mm, with an estimated growth rate of 6 mm per month. Most lesions demonstrated deep invasion (Clark level IV or V), and some exhibited perineural or perivascular infiltration. All lesions were surgically excised, except for one that was treated with radiotherapy. No regional recurrence or distant metastasis was observed during a median follow-up period of 9 months. Conclusions: Prolonged voriconazole therapy may increase the risk of aggressive cSCC in Japanese patients, even in the absence of prior transplantation. Early identification of phototoxic skin changes and prompt intervention are crucial to prevent deep tissue invasion and improve clinical outcomes.